Pazopanib is a new cancer drug that works by limiting the growth of new blood vessels in tumours. About half of patients who take pazopanib develop high blood pressure (hypertension). This side effect can make patients have to reduce or stop their cancer treatment, and can cause other health problems. The aim of this study is to find out exactly how the drug causes high blood pressure.

Patients will receive 800mg (2 X 400mg tablets) of pazopanib, to be administered once daily orally for 12 weeks or until development of hypertension (defined as VHyp), whichever occurs first.

Drug: Pazopanib

2 x 400mg pazopanib tablets taken once daily for 12 weeks

Other Name: Votrient

Detailed Description:

For this study, up to 52 patients with different cancer types will take pazopanib tablets for 12 weeks. They will visit the clinic every 1-2 weeks during treatment, and for a final safety check 4 weeks after stopping the drug (10 visits over 18 weeks).

At every visit, we will do a heart tracing, and check the patient's blood pressure and blood and urine chemicals (to check their health, and see if levels of these chemicals change). Patients will check their blood pressure at home every other day. They will also wear a blood pressure monitor for 24 hours on 3 occasions (during normal daily activities).

Patients will have 1 or 2 CT scans and 3 MRI scans during the study. On three occasions, a variety of specialised tests will measure how the patient's blood vessels are working.

Patients may choose to continue taking the drug after the 12 weeks of treatment, if their doctor feels it is appropriate.

Understanding how pazopanib causes high blood pressure will help us to advise doctors how to treat the high blood pressure effectively, so that patients can continue to take their cancer treatment safely. This research might also lead to the development of new cancer drugs in future, which do not cause this serious side effect.

Eligibility

Ages Eligible for Study:

18 Years and older (Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Patients must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up.

Patients with the following tumour types where VEGF inhibition would be appropriate therapy:

Measurable disease as per RECIST 1.1. A measurable lesion is defined as a lesion that can be accurately measured in at least one dimension with the longest diameter ≥ 20mm using conventional techniques. Patients with ovarian cancer or prostate cancer, where validated tumour markers (CA125 and PSA) are used clinically to monitor response, do not require measurable disease as per RECIST 1.1.

ECOG performance status 0 or 1.

Age ≥18 years.

Adequate organ system function

Female participant, or female partner of male participant, are of non-childbearing potential or agree to protocol-specified contraceptive measures

History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months

Prior major surgery or trauma within 28 days prior to first dose and/or presence of any non-healing wound, fracture, or ulcer.

Evidence of active bleeding or bleeding diathesis

Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage.

Note: Lesions infiltrating major pulmonary vessels (contiguous tumour and vessels) are excluded; however, the presence of a tumour that is touching, but not infiltrating (abutting) the vessels is acceptable (CT with contrast is strongly recommended to evaluate such lesions).

i) Large protruding endobronchial lesions in the main or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed.

ii) Lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of the bronchi are allowed.

Significant haemoptysis within 8 weeks prior to first dose of pazopanib (≥½ teaspoon of red blood within 8 weeks before first dose of study drug).

Any serious and/or pre-existing medical, psychiatric, or other condition that could interfere with patient's safety, provision of informed consent, or compliance to study procedures.

Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib and for the duration of the study.

Treatment with any of the following anti-cancer therapies:

a radiation therapy (single fraction radiotherapy for pain control is allowed in this period and when on study), surgery or tumour embolization within 14 days prior to the first dose of pazopanib OR b chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib c pazopanib or other antiangiogenic treatment (e.g. bevacizumab) within the past 12 weeks.

Administration of any non-oncologic investigational drug within 30 days or 5 half lives whichever is longer prior to receiving the first dose of study treatment.

Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia.

Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01392352

Locations

United Kingdom

Cambridge University Hospitals NHS Foundation Trust

Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ

Sponsors and Collaborators

Cambridge University Hospitals NHS Foundation Trust

University of Cambridge

GlaxoSmithKline

Investigators

Principal Investigator:

Duncan I Jodrell

University of Cambridge; honorary contract with Cambridge University Hospitals NHS Foundation Trust